We are studying the chemical nature of the ligand binding regions of particular myeloma proteins. These proteins are homogeneous and thus avoid the complication of the heterogeneity usually observed with induced antibodies. Studies are being done by subjecting myeloma proteins with such activity to controlled chemical alterations so that reactions taking place in the binding region can be distinguished from reactions taking place elsewhere on the molecule. The amino acid residues composing the binding region are being determined, as well as the position of these residues in the polypeptide chains which make up the protein. The nature of the ligand binding region of myeloma proteins will be compared with that of the combining sites of analogous antibodies induced by conventional methods. We have previously subjected such antibodies to extensive study. The comparison will include study of the microspecificity of the site as determined by the kinds of structure able to combine with the sites involved. Evidence is being sought for conformational changes which may take place when myeloma proteins bind ligand. Such changes have been shown by us to take place in antibody when its sites bind hapten.